347353-60-0Relevant academic research and scientific papers
Dihydropyrimidin-2(1H)-ones and dihydropyrimidin-2(1H)-thiones as inhibitors of sodium iodide symporter
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Paragraph 0062-0063, (2014/01/18)
The invention relates to novel dihydropyrimidin-2(1H)-ones and dihydropyrimidin-2(1H)-thiones of formula (I): for use as medicaments, and in particular as inhibitors of sodium iodide symporter (NIS) and reducers of iodine transport and/or accumulation into NIS-expressing cells. The invention also relates to a pharmaceutical composition comprising at least one compound of formula (I) as active principle. Finally, the present invention relates to specific dihydropyrimidin-2(1H)-ones and dihydropyrimidin-2(1H)-thiones of formula (I) as such.
DIHYDROPYRIMIDIN-2(1H)-ONES AND DIHYDROPYRIMIDIN-2(1H)-THIONES AS INHIBITORS OF SODIUM IODIDE SYMPORTER
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Page/Page column 18; 19, (2015/01/07)
The invention relates to novel dihydropyrimidin-2(lH)-ones and dihydropyrimidin- 2(lH)-thiones of formula (la). The invention also relates to the use of such compounds as medicaments, and in particular as inhibitors of sodium iodide symporter (NIS) and reducers of iodine transport and/or accumulation into NIS expressing cells. The invention also concerns a pharmaceutical composition comprising at least one compound of formula (la) as active principle.
Synthesis and Evaluation of 3,4-Dihydropyrimidin-2(1H)-ones as Sodium Iodide Symporter Inhibitors
Lacotte, Pierre,Puente, Celine,Ambroise, Yves
, p. 104 - 111 (2013/03/28)
The sodium iodide symporter (NIS) is responsible for the accumulation of iodide in the thyroid gland. This transport process is involved in numerous thyroid dysfunctions and is the basis for human contamination in the case of exposure to radioactive iodine species. 4-Aryl-3,4-dihydropyrimidin-2(1H)-ones were recently discovered by high-throughput screening as the first NIS inhibitors. Described herein are the synthesis and evaluation of 115 derivatives with structural modifications at five key positions on the pyrimidone core. This study provides extensive structure-activity relationships for this new class of inhibitors that will serve as a basis for further development of compounds with invivo efficacy and adequate pharmacokinetic properties. In addition, the SAR investigation provided a more potent compound, which exhibits an IC50 value of 3.2nM in a rat thyroid cell line (FRTL5).
